title: Development of lipid nanoparticles of diacerein, an antiosteoarthritic drug for enhancement in bioavailability and reduction in its side effects.
abstract: Osteoarthritis is the most common, multi component joint disease mainly characterized by destruction of articular cartilage which leads up to subchondral bone. Current treatment by NSAID's gives only symptomatic relief but semi-synthetic anthraquinone diacerein is novel chondroprotective agent intended for the treatment of osteoarthritis. Its active metabolite rhein inhibits the agents responsible for cartilage degradation. In the present study, stearic acid, long chain fatty acids, based solid lipid nanoparticles were prepared with enhanced oral bioavailability and lesser side effects. Diacerein loaded solid lipid nanoparticles were prepared by modified high shear homogenization with ultrasonication method using stearic acid as lipid. Pluronic F68 and soya lecithin was used as surfactant. Citric acid was added to give acidic environment to drug. Solid lipid nanoparticles were evaluated for different characterization parameters, in-vitro performance and in-vivo pharmacokinetics and anti-diarrhoeal study. Particle size of the diacerein loaded SLN was found in the range of 270 +/- 2.1 to 510 +/- 2.8 nm with zeta potential -13.78 +/- 3.4 mV to -19.66 +/- 2.1 mV. Maximum entrapment efficiency was achieved up to 88.1 +/- 1.3%. Surface and solid state characterization by TEM, XRD and DSC revealed that all particles are spherical in shape and drug entrapped inside lipid was in amorphous state. In-vitro release was done by dialysis bag method in phosphate buffer (pH 5.8) which showed controlled and extended release profile up to 12 hr. In-vivo pharmacokinetic study reveals an increase in Area Under Curve from 26.68 +/- 1.63 to 71.25 +/- 1.25 hr microg ml(-1). Further diarrhoeal side effect of diacerein was also found to reduce up to 37% by lipid nanoparticles. These results suggest that diacerein loaded solid lipid nanoparticles can be prepared efficiently with stearic acid and produces controlled and prolonged drug release profile. The oral bioavailability was enhanced by around 2.7 times and with lesser diarrhoeal side effects. These all will leads to overall improvement in patient compliance for the treatment.
authors.affiliation: Department of Pharmaceutics, Indian Institute of Technology, Banaras Hindu University, Varanasi 221005, UP, India.
authors.forename: Achint
authors.initials: A
authors.lastname: Jain
authors.forename: Sanjay Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Yuvraj
authors.initials: Y
authors.lastname: Singh
authors.forename: Sanjay
authors.initials: S
authors.lastname: Singh
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D016503:Drug Delivery Systems; D005260:Female; D008055:Lipids; D008297:Male; D053758:Nanoparticles; D010003:Osteoarthritis / Q000188:drug therapy*; D051381:Rats; D015854:Up-Regulation
chemical_list: D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; D008055:Lipids; C025292:diacerein